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The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range 0.03–81.9): Ongoing group, 41.8 (5.6–81.9); Decision group, 36.8 (4.0–70.1); Toxicity group, 30.6 (2.8–64.8); and progressive disease group, 2.0 (0.03–42.9). TFI in the Decision group was 15.1 months (0.6–61.6) and 30.6 months (2.8–64.8) in the Toxicity group. Long-term responses in R/M HNSCC patients treated with nivolumab are rare but gradually increasing. For this patient group, our best estimate of the optimal time to end treatment is 3 years, as the PFS in this study reached a plateau at that timepoint.

Background: Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. Methods: We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Results: Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Conclusions: Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.

Background: Few studies have reported on the etiology, severity, or device usage of unilateral sensorineural hearing loss (UHL) compared to bilateral hearing loss. Therefore, this study investigated the characteristics of UHL in adults and children. Methods: We performed a survey using questionnaires for secondary and tertiary otolaryngology institutions. Results: We included 15,981 patients (1549 children and 14,432 adults) from 196 institutions with otolaryngology residency programs and 2844 patients (336 children and 2508 adults) from 27 institutions with board members of the Japan Audiology Society. The latter submitted audiological data. Among children, most diagnoses were made at age 0. Approximately half of them had profound hearing loss, and 37 children (2.2%) used hearing devices. Among adults, the number of cases increased with age, but decreased when people reached their 80s and 90s. More than half of them had moderate hearing loss. Sudden sensorineural hearing loss was the most common cause of UHL of all ages; 4.4% of UHL patients used hearing devices, and most of the device users (98.6%) selected a conventional hearing aid. Conclusions: Hearing aid use is limited in children and adults with UHL in Japan. There could be many candidates with UHL for intervention such as a cochlear implant.

Background: There is no guideline for hearing compensation after temporal bone resection. This study aimed to retrospectively analyze surgical cases with reconstruction for hearing preservation after temporal bone malignancy resection and propose a new alternative to compensate for hearing loss. Methods: We retrospectively reviewed the medical records of 30 patients who underwent lateral temporal bone surgery for temporal bone malignancy at our institution and examined their hearing abilities after surgery. Result: The hearing outcomes of patients with an external auditory meatus reconstruction varied widely. The mean postoperative air–bone gap at 0.5, 1, 2, and 4 kHz ranged from 22.5 dB to 71.25 dB. On the other hand, the average difference between the aided sound field thresholds with cartilage conduction hearing aid and bone conduction thresholds at 0.5, 1, 2, and 4 kHz ranged from −3.75 to 41.25. More closely located auricular cartilage and temporal bone resulted in smaller differences between the aided sound field and bone conduction thresholds. Conclusions: There is still room for improvement of surgical techniques for reconstruction of the auditory meatus to preserve hearing after temporal bone resection. The cartilage conduction hearing aid may provide non-invasive postoperative hearing compensation after lateral temporal bone resection.

Pd nanoparticles were directly immobilized on acrylonitrile–butadiene–styrene copolymer (ABS), acrylonitrile–styrene copolymer (AS), polystyrene (PS), polyphenylene sulfide (PPS), poly(vinyl chloride) (PVC), polypropylene (PP), and polyethylene (PE) polymer substrates via chemical reactions induced by ionizing irradiation. X-ray photoelectron spectroscopy analysis revealed that the chemical state of the immobilized Pd nanoparticles depended on the polymer substrate type. Electroless plating was performed using the immobilized Pd nanoparticles as the catalyst, and Cu-plating films were deposited on all polymer substrates. The results of the tape-peeling test suggested that the chemical state of the immobilized Pd nanoparticles on the polymer substrates affected the plating adhesion strength. Notably, ABS with immobilized Pd particles exhibited a high adhesion strength beyond the practical level, even without prior chemical etching. It was presumed that the high adhesion strength was owing to the anchoring effect of the holes generated on the ABS surface by ionizing irradiation.

A new method has been developed to impart the antimicrobial activity of silver nanoparticles to resin substrates. A resin substrate immersed in an aqueous solution of silver nitrate was irradiated with gamma ray or high energy electron beams. Silver nanoparticles were successfully immobilized on the resin surface directly by chemical reactions induced by ionizing radiation. It was experimentally confirmed that various resin materials, such as acrylonitrile-butadiene-styrene, polyethylene, polypropylene, polyvinyl chloride, and polycarbonate, were applicable for this process. The effects of gamma ray or electron beam irradiation on resin substrates were almost negligible since the irradiation dose was equal or less than that used for sterilization. Despite the small amount of Ag loadings, the obtained samples showed high antibacterial and antiviral activities.

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

Background: Accurate data on the prevalence of hearing impairment and severity across age and gender are paramount to formulate hearing health policies. Here, we sought to analyze audiometric data from a large group of age-diverse people in Japan, which has not been previously described in detail. Methods: We analyzed retrospective hearing threshold data of 23,860 participants (10–99 years; left-right hearing threshold difference

COVID-19 often causes sequelae after initial recovery, referred to collectively as long COVID. Long COVID is considered to be caused by the persistence of chronic inflammation after acute COVID-19 infection. We found that all long COVID patients had residual inflammation in the epipharynx, an important site of coronavirus replication, and some long COVID symptoms are similar to those associated with chronic epipharyngitis. Epipharyngeal abrasive therapy (EAT) is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. In this study, we evaluated the efficacy of EAT for the treatment of long COVID. The subjects in this study were 58 patients with long COVID who were treated with EAT in the outpatient department once a week for one month (mean age = 38.4 ± 12.9 years). The intensities of fatigue, headache, and attention disorder, which are reported as frequent symptoms of long COVID, were assessed before and after EAT using the visual analog scale (VAS). EAT reduced inflammation in the epipharynx and significantly improved the intensity of fatigue, headache, and attention disorder, which may be related to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These results suggest that EAT has potential as a novel method for long COVID treatment.

Pd nanoparticles were immobilized on an acrylonitrile–butadiene–styrene copolymer (ABS) substrate using ionizing radiation. The samples were prepared by irradiating plastic zipper packs containing ABS substrates and a Pd(NO3)2 aqueous solution with a high-energy electron beam (4.8 MeV). Pd nanoparticles immobilized on the ABS substrate surfaces were observed using scanning electron microscopy (SEM). The chemical state of Pd was found to be coordinated to a carbonyl group or a metallic state by X-ray photoelectron spectroscopy (XPS) measurements. The peel strength of the Cu film on the Pd/ABS samples was 0.7 N/mm or higher. This result shows that the prepared Pd/ABS samples have high adhesion strength, despite not undergoing treatments such as etching with chromic acid. This method is expected to immobilize metal nanoparticles, not only on plastic plates but also on various other materials.

Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in AT. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor’s niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.

Currently, only lateral temporal bone resection (LTBR) and subtotal temporal bone resection (STBR) are widely utilized for the surgical treatment of advanced squamous cell carcinoma of the external auditory canal (EAC-SCC). However, there are few descriptions of variations on these surgical approaches. This study aimed to elucidate the variations of en bloc resection for advanced EAC-SCC. We dissected the four sides of cadaveric heads to reveal the anatomical structures related to temporal bone resection. From the viewpoint of surgical anatomy, surgical patterns of temporal bone cutting can be divided into four categories: conventional LTBR, extended LTBR, conventional STBR, and modified STBR. Extended LTBR is divided into four types: superior, inferior, anterior, and posterior extensions. Several extension procedures can be combined based on the extension of the tumor. Furthermore, en bloc resection with the temporomandibular joint or glenoid fossa increases the technical difficulty of a surgical procedure because the exposure and manipulation of the petrous segment of the internal carotid artery are limited from the middle cranial fossa. Surgical approaches for advanced SCC of the temporal bone are diverse. They require accurate preoperative evaluation of the tumor extension and preoperative consideration of the exact line of resection to achieve marginal negative resection.

d-amino acids have distinct roles from their l-enantiomer. In particular, some d-amino acids function as agonists or antagonists of neuronal receptors and are involved in higher brain functions. Thus, it is important to precisely measure the levels of these amino acid enantiomers in cells and tissues. Various quantification methods have been developed for measurements of chiral amino acids. However, each method has advantages and disadvantages. Additionally, measuring the amino acid enantiomers in crude biological samples requires a higher selectivity. In this study, we developed a quantification method for amino acid enantiomers using derivatization with Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA) followed by liquid chromatography–tandem mass spectrometry (LC/MS/MS) with a conventional reversed-phase column. We simultaneously identified 10 chiral amino acids. Furthermore, we applied this method to investigate murine tissue samples and examined the effect of aging on the amino acid levels in aged brain regions. We found that aging decreased the levels of both d-serine and d-aspartate in the hippocampus. In addition, d-Phenylalanine in the thalamus significantly increased with age. In conclusion, our method is suitable for the quantification of the d-amino acids in crude biological samples and may contribute to elucidating the biological roles of chiral amino acids.

Recent studies have suggested the benefit of salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively examined the outcome of SCT and the usefulness of the serum C-reactive protein level (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Thirty-nine patients with R/M HNSCC were enrolled in this study. Twenty-five patients (64.1%) received combination chemotherapy of weekly paclitaxel and cetuximab (PC) as SCT, and 14 patients (35.9%) received tegafur-gimestat-otastat potassium (S1), an oral fluoropyrimidine. In all patients, the response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 45.2%, 85.7%, 6.5 months, and 13.5 months, respectively. No chemotherapy-related deaths were observed. These PC groups had low CRP (p = 0.0440, p = 0.0354). A multivariate analysis also showed that a lower CRP value was significantly associated with a better OS (p = 0.0078). We clarified the usefulness of the PC and S1 regimens as SCT. In addition, SCT with the PC regimen showed a better prognosis with a lower CRP or NLR at induction than a higher CRP or NLR. This is the first report on biomarkers of SCT in R/M HNSCC.